Sodium glucose-like transporter-2 inhibitor (SGLT2i) drugs are widely prescribed in type 2 diabetes (T2DM). They inhibit glucose reabsorption, inducing glycosuria. They also induce euglycaemic diabetic ketoacidosis (EDKA) at a rate of 0.1%, the mechanism for which is unclear.

Rafey et al. describe two patients with T2DM who developed EDKA on SGLT2i post-operatively. They required 92 hours of treatment compared with a mean 35 hours in DKA in T1DM. Potential mechanisms include impairment by SGLT2i of ketone excretion (unlikely as both patients had marked ketonuria) or complete β-cell failure (although one patient was on basal bolus insulin as well as SGLT2i). SGLT2i stimulates α-cell glucagon production which decreases insulin, suggesting a mechanism for insulin deficiency. Both patients had undergone surgery, which itself causes reduced insulin sensitivity and may have contributed. The authors suggest stopping SGLT2i 48 hours before surgery. In addition, low dose insulin infusion was used, and maybe a higher dose of insulin could be considered, with glucose infusion, to inhibit ketogenesis.

More detailed mechanistic information is needed, including insulin, glucagon, urine and blood ketones throughout an episode of EDKA, to achieve a greater understanding of the mechanism of this rare but serious complication of SGLT2i use.

Read the full article in Endocrinology, Diabetes & Metabolism Case Reports 19-0087